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Antioxidants
1. What are antioxidants?
Antioxidants are substances that may protect cells from the damage caused by unstable molecules
known as free radicals. Free radical damage may lead to cancer. Antioxidants interact with and
stabilize free radicals and may prevent some of the damage free radicals otherwise might cause.
Examples of antioxidants include beta-carotene, lycopene, vitamins C, E, and A, and other substances.
2. Can antioxidants prevent cancer?
Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that
antioxidants may slow or possibly prevent the development of cancer. However, information from
recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached
inconsistent conclusions.
3. What was shown in previously published large-scale clinical trials?
Five large-scale clinical trials published in the 1990s reached differing conclusions about the effect of
antioxidants on cancer. The studies examined the effect of beta-carotene and other antioxidants on
cancer in different patient groups. However, beta-carotene appeared to have different effects
depending upon the patient population. The conclusions of each study are summarized below.
• The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer
Prevention Study, published in 1993. This trial investigated the effect of a combination of beta-
carotene, vitamin E, and selenium on cancer in healthy Chinese men and women at high risk for
gastric cancer. The study showed a combination of beta-carotene, vitamin E, and selenium
significantly reduced incidence of both gastric cancer and cancer overall. (1)
• A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitmain E)/Beta-Carotene Cancer
Prevention Study (ATBC) demonstrated that lung cancer rates of Finnish male smokers increased
significantly with beta-carotene and were not affected by vitamin E. (2)
• Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET), also
demonstrated a possible increase in lung cancer associated with antioxidants. (3)
• The 1996 Physicians' Health Study I (PHS) found no change in cancer rates associated with beta-
carotene and aspirin taken by U.S. male physicians. (4)
• The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene in the
prevention of cancer and cardiovascular disease among women age 45 years or older. Among
apparently healthy women, there was no benefit or harm from beta-carotene supplementation.
Investigation of the effect of vitamin E is ongoing. (5)
4. Are antioxidants under investigation in current large-scale clinical trials?
Three large-scale clinical trials continue to investigate the effect of antioxidants on cancer. The
objective of each of these studies is described below. More information about clinical trails can be
obtained using cancer.gov/clinicaltrials, www.clinicaltrials.gov, or the CRISP database at www.nih.gov.
• The Women's Health Study (WHS) is currently evaluating the effect of vitamin E in the primary
prevention of cancer among U.S. female health professionals age 45 and older. The WHS is expected
to conclude in August 2004.
• The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the United States,
Puerto Rico, and Canada. SELECT is trying to find out if taking selenium and/or vitamin E supplements
can prevent prostate cancer in men age 50 or older. The SELECT trial is expected to stop recruiting
patients in May 2006.
• The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name.
The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total
cancer incidence. The PHS II is expected to conclude in August 2007.
5. Will NCI continue to investigate the effect of beta-carotene on cancer?
Given the unexpected results of ATBC and CARET, and the finding of no effect of beta-carotene in the
PHS and WHS, NCI will follow the people who participated in these studies and will examine the long-
term health effects of beta-carotene supplements. Post-trial follow-up has already been funded by NCI
for CARET, ATBC, the Chinese Cancer Prevention Study, and the two smaller trials of skin cancer and
colon polyps. Post-trial follow-up results have been published for ATBC, and as of July 2004 are in
press for CARET and are in progress for the Chinese Cancer Prevention Study.
6. How might antioxidants prevent cancer?
Antioxidants neutralize free radicals as the natural by-product of normal cell processes. Free radicals
are molecules with incomplete electron shells which make them more chemically reactive than those
with complete electron shells. Exposure to various environmental factors, including tobacco smoke
and radiation, can also lead to free radical formation. In humans, the most common form of free
radicals is oxygen. When an oxygen molecule (O2) becomes electrically charged or "radicalized" it
tries to steal electrons from other molecules, causing damage to the DNA and other molecules. Over
time, such damage may become irreversible and lead to disease including cancer. Antioxidants are
often described as "mopping up" free radicals, meaning they neutralize the electrical charge and
prevent the free radical from taking electrons from other molecules.
7. Which foods are rich in antioxidants?
Antioxidants are abundant in fruits and vegetables, as well as in other foods including nuts, grains
and some meats, poultry and fish. The list below describes food sources of common antioxidants.
• Beta-carotene is found in many foods that are orange in color, including sweet potatoes, carrots,
cantaloupe, squash, apricots, pumpkin, and mangos. Some green leafy vegetables including collard
greens, spinach, and kale are also rich in beta-carotene.
• Lutein, best known for its association with healthy eyes, is abundant in green, leafy vegetables
such as collard greens, spinach, and kale.
• Lycopene is a potent antioxidant found in tomatoes, watermelon, guava, papaya, apricots, pink
grapefruit, blood oranges, and other foods. Estimates suggest 85 percent of American dietary intake
of lycopene comes from tomatoes and tomato products.
• Selenium is a mineral, not an antioxidant nutrient. However, it is a component of antioxidant
enzymes. Plant foods like rice and wheat are the major dietary sources of selenium in most countries.
The amount of selenium in soil, which varies by region, determines the amount of selenium in the
foods grown in that soil. Animals that eat grains or plants grown in selenium-rich soil have higher
levels of selenium in their muscle. In the United States, meats and bread are common sources of
dietary selenium. Brazil nuts also contain large quantities of selenium.
• Vitamin A is found in three main forms: retinol (Vitamin A1), 3,4-didehydroretinol (Vitamin A2), and 3-
hydroxy-retinol (Vitamin A3). Foods rich in vitamin A include liver, sweet potatoes, carrots, milk, egg
yolks and mozzarella cheese.
• Vitamin C is also called ascorbic acid, and can be found in high abundance in many fruits and
vegetables and is also found in cereals, beef, poultry and fish.
• Vitamin E, also known as alpha-tocopherol, is found in almonds, in many oils including wheat germ,
safflower, corn and soybean oils, and also found in mangos, nuts, broccoli and other foods.
References:
1)Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with
specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general
population. J Natl Cancer Inst 1993;85:1483-91.
2)The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effects of vitamin E and
beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;
330:1029-35.
3)Omenn GS, Goodman G, Thomquist M, et al. The beta-carotene and retinol efficacy trial (CARET) for
chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.
Cancer Res 1994;54(7 Suppl):2038s-43s.
4)Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-
term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular
disease. N Engl J Med 1996;334:1145-9.
5)Lee IM, Cook NR, Manson JE. Beta-carotene supplementation and incidence of cancer and
cardiovascular disease: Women's Health Study. J Natl Cancer Inst 1999;91:2102-6.
Antioxidants are substances that may protect cells from the damage caused by unstable molecules
known as free radicals. Free radical damage may lead to cancer. Antioxidants interact with and
stabilize free radicals and may prevent some of the damage free radicals otherwise might cause.
Examples of antioxidants include beta-carotene, lycopene, vitamins C, E, and A, and other substances.
2. Can antioxidants prevent cancer?
Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that
antioxidants may slow or possibly prevent the development of cancer. However, information from
recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached
inconsistent conclusions.
3. What was shown in previously published large-scale clinical trials?
Five large-scale clinical trials published in the 1990s reached differing conclusions about the effect of
antioxidants on cancer. The studies examined the effect of beta-carotene and other antioxidants on
cancer in different patient groups. However, beta-carotene appeared to have different effects
depending upon the patient population. The conclusions of each study are summarized below.
• The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer
Prevention Study, published in 1993. This trial investigated the effect of a combination of beta-
carotene, vitamin E, and selenium on cancer in healthy Chinese men and women at high risk for
gastric cancer. The study showed a combination of beta-carotene, vitamin E, and selenium
significantly reduced incidence of both gastric cancer and cancer overall. (1)
• A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitmain E)/Beta-Carotene Cancer
Prevention Study (ATBC) demonstrated that lung cancer rates of Finnish male smokers increased
significantly with beta-carotene and were not affected by vitamin E. (2)
• Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET), also
demonstrated a possible increase in lung cancer associated with antioxidants. (3)
• The 1996 Physicians' Health Study I (PHS) found no change in cancer rates associated with beta-
carotene and aspirin taken by U.S. male physicians. (4)
• The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene in the
prevention of cancer and cardiovascular disease among women age 45 years or older. Among
apparently healthy women, there was no benefit or harm from beta-carotene supplementation.
Investigation of the effect of vitamin E is ongoing. (5)
4. Are antioxidants under investigation in current large-scale clinical trials?
Three large-scale clinical trials continue to investigate the effect of antioxidants on cancer. The
objective of each of these studies is described below. More information about clinical trails can be
obtained using cancer.gov/clinicaltrials, www.clinicaltrials.gov, or the CRISP database at www.nih.gov.
• The Women's Health Study (WHS) is currently evaluating the effect of vitamin E in the primary
prevention of cancer among U.S. female health professionals age 45 and older. The WHS is expected
to conclude in August 2004.
• The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the United States,
Puerto Rico, and Canada. SELECT is trying to find out if taking selenium and/or vitamin E supplements
can prevent prostate cancer in men age 50 or older. The SELECT trial is expected to stop recruiting
patients in May 2006.
• The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name.
The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total
cancer incidence. The PHS II is expected to conclude in August 2007.
5. Will NCI continue to investigate the effect of beta-carotene on cancer?
Given the unexpected results of ATBC and CARET, and the finding of no effect of beta-carotene in the
PHS and WHS, NCI will follow the people who participated in these studies and will examine the long-
term health effects of beta-carotene supplements. Post-trial follow-up has already been funded by NCI
for CARET, ATBC, the Chinese Cancer Prevention Study, and the two smaller trials of skin cancer and
colon polyps. Post-trial follow-up results have been published for ATBC, and as of July 2004 are in
press for CARET and are in progress for the Chinese Cancer Prevention Study.
6. How might antioxidants prevent cancer?
Antioxidants neutralize free radicals as the natural by-product of normal cell processes. Free radicals
are molecules with incomplete electron shells which make them more chemically reactive than those
with complete electron shells. Exposure to various environmental factors, including tobacco smoke
and radiation, can also lead to free radical formation. In humans, the most common form of free
radicals is oxygen. When an oxygen molecule (O2) becomes electrically charged or "radicalized" it
tries to steal electrons from other molecules, causing damage to the DNA and other molecules. Over
time, such damage may become irreversible and lead to disease including cancer. Antioxidants are
often described as "mopping up" free radicals, meaning they neutralize the electrical charge and
prevent the free radical from taking electrons from other molecules.
7. Which foods are rich in antioxidants?
Antioxidants are abundant in fruits and vegetables, as well as in other foods including nuts, grains
and some meats, poultry and fish. The list below describes food sources of common antioxidants.
• Beta-carotene is found in many foods that are orange in color, including sweet potatoes, carrots,
cantaloupe, squash, apricots, pumpkin, and mangos. Some green leafy vegetables including collard
greens, spinach, and kale are also rich in beta-carotene.
• Lutein, best known for its association with healthy eyes, is abundant in green, leafy vegetables
such as collard greens, spinach, and kale.
• Lycopene is a potent antioxidant found in tomatoes, watermelon, guava, papaya, apricots, pink
grapefruit, blood oranges, and other foods. Estimates suggest 85 percent of American dietary intake
of lycopene comes from tomatoes and tomato products.
• Selenium is a mineral, not an antioxidant nutrient. However, it is a component of antioxidant
enzymes. Plant foods like rice and wheat are the major dietary sources of selenium in most countries.
The amount of selenium in soil, which varies by region, determines the amount of selenium in the
foods grown in that soil. Animals that eat grains or plants grown in selenium-rich soil have higher
levels of selenium in their muscle. In the United States, meats and bread are common sources of
dietary selenium. Brazil nuts also contain large quantities of selenium.
• Vitamin A is found in three main forms: retinol (Vitamin A1), 3,4-didehydroretinol (Vitamin A2), and 3-
hydroxy-retinol (Vitamin A3). Foods rich in vitamin A include liver, sweet potatoes, carrots, milk, egg
yolks and mozzarella cheese.
• Vitamin C is also called ascorbic acid, and can be found in high abundance in many fruits and
vegetables and is also found in cereals, beef, poultry and fish.
• Vitamin E, also known as alpha-tocopherol, is found in almonds, in many oils including wheat germ,
safflower, corn and soybean oils, and also found in mangos, nuts, broccoli and other foods.
References:
1)Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with
specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general
population. J Natl Cancer Inst 1993;85:1483-91.
2)The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effects of vitamin E and
beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;
330:1029-35.
3)Omenn GS, Goodman G, Thomquist M, et al. The beta-carotene and retinol efficacy trial (CARET) for
chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.
Cancer Res 1994;54(7 Suppl):2038s-43s.
4)Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-
term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular
disease. N Engl J Med 1996;334:1145-9.
5)Lee IM, Cook NR, Manson JE. Beta-carotene supplementation and incidence of cancer and
cardiovascular disease: Women's Health Study. J Natl Cancer Inst 1999;91:2102-6.
NCP Miracle II
161 Richardson-Bass Rd
Kenly, NC 27542
Tel:(919)284-6002 Fax:(919)284-4197
EMail: info1@ncpmiracle2.com
161 Richardson-Bass Rd
Kenly, NC 27542
Tel:(919)284-6002 Fax:(919)284-4197
EMail: info1@ncpmiracle2.com
